2019年NCCN口腔口咽癌诊疗指南更新解读

美国癌症联合委员会2017年第8版《AJCC肿瘤分期手册》出版,口腔及口咽癌TNM分期标准中新增侵袭深度（DOI）、淋巴结外扩展（ENE）、人乳头瘤病毒（HPV）等指标,并将口咽癌分为HPV阳性（p16+）与HPV阴性（p16-）,分别制定了不同的TNM分期标准。2018年,美国国立综合癌症网（NCCN）首次为HPV阳性（p16+）口咽癌制定了诊疗指南。2019年第1版NCCN头颈癌诊疗指南已经发布,其中对口腔口咽癌指南做了部分修订。为临床工作需要,本文结合2版变化进行部分解读。     

68例HPV相关口咽鳞癌患者生存分析

目的 探讨口咽癌HPV适用检测方法并比较HPV阳性患者新、旧版肿瘤TNM分期降级后的预后差异,为指导HPV相关口咽癌的精准诊疗提供临床依据。方法 对171例口咽鳞状细胞癌（简称鳞癌）患者,分别行脱落细胞学、P16免疫组织化学及HPV-RNA PCR检测HPV,比较3种检测方法的结果。分析68例HPV相关口咽鳞癌患者的临床及病理资料,根据新、旧版TNM分期标准对其重新分期,了解降级情况,统计各期患者生存率,比较新、旧2版分期患者的预后,应用 Kaplan-Meier方法建模,采用SPSS 22.0 软件包进行统计学分析。结果 免疫组织化学P16检测、口咽脱落细胞检测和PCR检测的口咽癌HPV阳性检出率分别为25.7%、14.6%和24.0%,脱落细胞检测与其他2种检测均有统计学差异（P=0.000）,免疫组织化学和PCR检测无统计学差异（P=0.205）。68例HPV阳性口咽鳞癌患者按照第7版与第8版TNM标准分期,分别为Ⅰ期3和42例,Ⅱ期7和14例,Ⅲ期17和9例,Ⅳ期41和3例。第7版与8版分期患者3年生存率比较,Ⅰ期100.0%和89.7%（P=0.672）,Ⅱ期68.6%和61.9%（P=0.961）,Ⅲ期66.8%和37.0%（P= 0.043）,Ⅳ期74.8%和0.00%（P=0.000）。第7与8版分期的早期患者（Ⅰ、Ⅱ期）生存率比较,78.8%和82.7%（P=0.585）,晚期患者（Ⅲ、Ⅳ期）生存率比较,71.2%和27.8%（P =0.000）。HPV阳性患者按照第7版分期,早期与晚期患者生存率为78.8%和71.2%（P=0.982）;按照8版分期,早期与晚期患者生存率为82.7%和27.8%（P=0.000）。结论 脱落细胞检查不宜作为诊断HPV阳性口咽鳞癌的单一标准,P16免疫组织化学检测和PCR基因检测各有优缺点,应根据实际情况选择。对于HPV阳性口咽鳞癌患者,新版分期更符合临床实际情况,预后分层更加清晰,能更好指导临床决策,值得临床推广应用。     

ASCO指南解读：“口腔和口咽鳞状细胞癌颈部管理”

为提供口腔和口咽鳞状细胞癌颈部管理的循证建议,美国临床肿瘤协会（ASCO）成立了专家组,对1990—2018年相关文献进行了分析,包括系统评价、荟萃分析、随机对照试验、前瞻性和回顾性观察对照试验。共纳入124篇,形成2019版指南。该指南设定了6种常见临床情形,其中口腔和口咽鳞状细胞癌各3种。从生存率、疾病控制情况、复发率及生存质量等角度,讨论了高质量颈淋巴清扫术、术后辅助放疗或放化疗、手术或非手术治疗的适应证,以及单独放化疗是否充足等问题,分条依次提出临床治疗建议。对多种慢性病患者、指南的局限性和适用范围也进行了阐述。本文就2019版ASCO指南进行解读,为诊治口腔颌面部肿瘤提供临床指导。     

P16蛋白在口咽癌和口腔癌中的表达及临床意义

目的:分析口咽癌和口腔癌中P16蛋白表达情况及临床意义.方法:采用免疫组织化学染色法检测70例口咽癌和60例口腔癌中P16蛋白的表达情况,分析其与患者临床病理学指标的相关性及临床意义.结果:口咽癌中P16蛋白的阳性率为22.9％(16/70),与P16阴性组相比,患者的年龄、吸烟、病理分化、N分期和TNM临床分期具有统计学意义(P＜0.05);口腔癌中P16蛋白的阳性率为8.3％ (5/60),与P16阴性组相比,病理分化和TNM临床分期有统计学意义(P＜0.05).结论:口咽癌中P16蛋白阳性率明显高于口腔癌,HPV感染是口咽癌和口腔癌不可忽视的诱发因素.     

336例HPV相关性与非相关性口咽鳞癌患者生存分析

目的: 分析比较HPV相关性与非相关性口咽鳞癌（oropharyngeal squamous cell carcinoma,OPSCC）患者在新、旧版TNM不同分期情况下,患者生存及预后差异,为OPSCC的治疗策略与预后评估提供临床依据。方法: 收集2010年1月—2016年12月青岛大学附属医院手术治疗的原发OPSCC患者,采用p16免疫组织化学检测方法对病理标本重新进行评估,统计患者生存信息,并分别运用第7版、第8版TNM分期系统对肿瘤进行分期,记录新、旧版的降级情况,分析、比较HPV相关性与非相关性OPSCC患者两版不同分期对生存率及预后的影响。采用SPSS 25.0软件包对数据进行统计学分析。结果: 最终纳入336例OPSCC患者,其中HPV相关性OPSCC患者101例（30.1%）,5年生存率为47.5%（48/101）,中位生存时间58个月;非相关性OPSCC患者5年生存率为34.0%（80/235）,中位生存时间37个月。HPV相关性OPSCC患者第8版TNM分期与第7版TNM分期对比,其总体降级率为77.2%（78/101）,晚期患者降级率为100%（69/69）,晚期患者中降至早期的患者占比69.6%（48/69）。结论: HPV相关性OPSCC患者的生存率和生存中位时间明显优于非相关性OPSCC患者,第8版TNM分期手册的OPSCC分期相比第7版更符合临床实际,预后分层更加清晰,能更好指导临床决策。     

口腔癌及口咽癌病理诊断规范

口腔癌及口咽癌是口腔颌面部最常见的恶性肿瘤。规范化的口腔癌及口咽癌病理诊断报告不仅应提供给临床准确的病理诊断,还应包括与患者预后评估、治疗策略选择相关的信息。由中华口腔医学会口腔病理学专业委员会牵头组织成立专家组,对口腔癌及口咽癌病理标本固定、取材及报告内容等进行研讨与规范,形成《口腔癌及口咽癌病理诊断规范》。此规范涵盖了近年来在口腔癌和口咽癌临床病理方面的一些重要变化,如口腔癌肿瘤T分期应考虑肿瘤侵袭深度、肿瘤N分期应考虑有无淋巴结外扩展、口咽癌中新亚型人乳头状瘤病毒相关性鳞状细胞癌等。希望通过本规范的制定,提高我国口腔癌及口咽癌病理报告质量,为临床治疗及预后评估提供依据。     

口腔癌及口咽癌病理诊断规范

口腔癌及口咽癌是口腔颂面部最常见的恶性肿瘤。规范化的口腔癌及口咽癌病理诊断报告不仅应提供给临床准确的病理诊断,还应包括与患者预后评估、治疗策略选择相关的信息。由中华口腔医学会口腔病理学专业委员会牵头组织成立专家组,对口腔癌及口咽癌病理标本固定、取材及报告内容等进行研讨与规范,形成《口腔癌及口咽癌病理诊断规范》。此规范涵盖了近年来在口腔癌和口咽癌临床病理方面的一些重要变化,如口腔癌肿瘤T分期应考虑肿瘤侵袭深度、肿瘤N分期应考虑有无淋巴结外扩展、口咽癌中新亚型人乳头状瘤病毒相关性鳞状细胞癌等。希望通过本规范的制定,提高我国口腔癌及口咽癌病理报告质量,为临床治疗及预后评估提供依据。     

NCCN头颈癌诊治指南（2007版）（6）

2002年美国癌症联合会（AJCC）咽（包括舌根、软腭和腭垂）癌TNM分期系统     

口腔癌浸润深度对改进肿瘤TNM分期及预后评价的影响

目的:分析比较美国癌症联合委员会(AJCC)第8版与第7版TNM分期系统在口腔癌临床治疗决策、预后分层以及提高预后评价准确性中的意义.方法:收集2009年1月—2015年6月手术治疗的原发口腔鳞状细胞癌患者,分别应用第7版、第8版TNM分期系统对肿瘤进行分期,比较2种分期的变化情况.采用SPSS 26.0软件包,运用K...     

人类乳头瘤病毒阳性口咽癌对放疗敏感的研究进展

口咽癌(oropharyngeal carcinoma)是一种高度异质性疾病,其主要病因是烟草、酒精的滥用或高危人类乳头瘤病毒(human papillomavirus,HPV)感染的结果。HPV阳性口咽癌与HPV阴性口咽癌存在明显的病因、流行病学、预后等方面的差异,因此治疗上应采取不同的方法。目前已知HPV阳性口咽癌对放射治疗敏感,认为其对放疗敏感可能通过多种机制共同完成。HPV阳性口咽癌存在低表达的野生肿瘤蛋白p35(tumor protein p53,TP53)基因,放射治疗可通过DNA双链断裂损伤方式激活p53并诱导细胞发生凋亡;细胞对DNA损伤存在常见的非同源末端连接(non?homologous end joining,NHEJ)修复路径,HPV癌蛋白抑制该路径可使肿瘤对放疗更为敏感;此外,免疫应答在放疗作用下进一步激活也参与对肿瘤的消除作用。本文就HPV阳性口咽癌对放疗敏感的研究进行综述,为未来临床上针对口咽癌不同致病因素及临床分期采取针对性的治疗手段提供科学依据。     

An update on squamous carcinoma of the oral cavity, oropharynx, and maxillary sinus

There are more than 45,000 new cancer cases involving the head and neck diagnosed each year within the United States. Squamous cell carcinoma accounts for the majority of cases, often occurring within the oral cavity and oropharynx. This article reviews current literature and various controversial topics involving the diagnosis and treatment strategies for patients with oral cavity/oropharyngeal cancers. Although not considered cancer within the oral cavity, maxillary sinus squamous cell carcinoma is discussed.     

The connection between human papillomavirus and oropharyngeal squamous cell carcinomas in the United States: implications for dentistry

BackgroundResults from studies conducted in the past several years suggest that some oropharyngeal cancers, those of the base of the tongue and the tonsils, are associated with high-risk types of human papillomavirus (HPV). In this article, the authors summarize the availabel evidence regarding the epidemiology of HPV-associated oropharyngeal cancers in the United States, the availabel HPV vaccines and the implications of these for dentistry. They also examine the differences in HPV prevalence between cancers of the oral cavity and those of the oropharynx.Types of Studies ReviewedThe authors searched PubMed, Web of Science, The Cochrane Library and the National Guideline Clearinghouse to identify English-language systematic reviews and meta-analyses focused on HPV-associated oropharyngeal squamous cell cancers published from January 2005 through May 2011.ResultsMolecular and epidemiologic evidence suggest a strong etiologic association of HPV with oropharyngeal cancers. The incidence of oropharyngeal cancers in the United States has increased between 1973 and 2007, whereas that of cancers at other head and neck sites has decreased steadily. Compared with HPV-negative cancers, HPV-positive oropharyngeal cancers are associated with certain sexual behaviors, occur more often among white men and people who do not use tobacco or alcohol, and may occur in a population younger by about four years (median ages, 52–56 years). Despite often having a later stage of diagnosis, people with HPV-positive oropharyngeal cancers have a lower risk of dying or recurrence than do those with HPV-negative cancers. The effectiveness of the HPV vaccine in preventing oropharyngeal cancers is unknown.Clinical ImplicationsDental health care personnel (DHCP) should be knowledgeable about the role of HPV in carcinogenesis, the association of HPV with oropharyngeal cancers and HPV vaccines, and they should be prompt in referring patients with suggestive symptoms for evaluation. DHCP can play an important role in increasing patients’ knowledge about HPV and oropharyngeal cancers.     

The role of the human papillomavirus in oropharyngeal cancer

In recent years there has been an overall decrease in cancers of the oral cavity, and a concurrent increase in cancers in specific sites of the posterior oral cavity and oropharynx in the United States. There is increasing evidence that the human papillomavirus may play a role in the development of oropharyngeal squamous cell carcinoma. In this article we review the biology and risk factors associated with HPV and oropharyngeal carcinoma, and recent data suggesting that this type of cancer may be unique in its response to treatment and prognosis.     

The role of the human papillomavirus in oropharyngeal cancer

In recent years there has been an overall decrease in cancers of the oral cavity, and a concurrent increase in cancers in specific sites of the posterior oral cavity and oropharynx in the United States. There is increasing evidence that the human papillomavirus (HPV) may play a role in the development of oropharyngeal squamous cell carcinoma. In this article we review the biology and risk factors associated with HPV and oropharyngeal carcinoma, and recent data suggesting that this type of cancer may be unique in its response to treatment and prognosis.     

Declining oral cancer rates in Sri Lanka: are we winning the war after being at the top of the cancer league table?

Oral Diseases (2011) 17 , 636–641 Objectives: To investigate the age‐standardized incidence, demography, recent trends and patterns of incidence of oral cancer in Sri Lanka between 1985 and 2005. Materials and methods: Data on oral and oropharyngeal cancers were obtained from the published hospital‐based cancer registry reports in the years 1985, 1990, 1995, 2000, and 2005. The data were analyzed by gender, age (<40 or >40 years), and by site. A linear regression analysis was performed on the age‐standardized oral and oropharyngeal cancer incidence rates to examine the trends over a 20‐year period. Results: There was a steady decline in the age‐standardized incidence of lip and oral cavity cancers over the past 20 years in both men and women. A significant reduction of 1.9% per year is noted over this period. Contrary to this, cancers of the oropharynx (C09, C10, and C14) showed a slight increase over the same period. Conclusions: Reversal of betel quid use and smoking must be considered in accounting for declining trends for oral cancer. Increasing rates of oropharyngeal cancer raises the issue whether risk factors for the oropharynx are different to those of the oral cavity, and this may need further investigation.